Fabrication of an ultra-high quality MgF2 micro-resonator for a single soliton comb generation.

Crystalline micro-resonators are attractive for a wide range of applications due to their extremely high quality (Q) factor. In this paper, we develop a semi-automatic method for fabricating ultra-high Q-factor MgF2 crystalline micro-resonators. By utilizing a force feedback sensor and corresponding control, we made a semi-automatic precision grind-and-polishing machine, and successfully fabricated trapezoid MgF2 resonators with diameter of 9.5 mm and a root mean square surface roughness of 0.26 nm. The maximum difference of peaks and valleys is about 1.5 nm. The Q-factor was characterized to be 9.24 × 109at 1550 nm by the cavity ring-down spectroscopy. A single soliton optical frequency comb was generated by pumping the microcavity with 150 mW optical power.

Widely separated optical Kerr parametric oscillation in AlN microrings.

Here, we report $ {\chi ^{(3)}} $χ(3)-based optical parametric oscillation (OPO) with widely separated signal-idler frequencies from crystalline aluminum nitride microrings pumped at $ 2\,\,\unicode{x00B5}{\rm m} $2µm. By tailoring the width of the microring, OPO reaching toward the telecom and mid-infrared bands with a frequency separation of 64.2 THz is achieved. While dispersion engineering through changing the microring width is capable of shifting the OPO sideband by $ \gt {9}\;{\rm THz}$>9THz, the OPO frequency can also be agilely tuned in the ranges of 1 and 0.1 THz, respectively, by shifting the pump wavelength and controlling the chip's temperature. At high pump powers, the OPO sidebands further evolve into localized frequency comb lines. Such large-frequency-shift OPO with flexible wavelength tunability will lead to enhanced chip-scale light sources.

Ultraviolet to mid-infrared supercontinuum generation in single-crystalline aluminum nitride waveguides.

We demonstrate ultrabroadband supercontinuum generation from ultraviolet to mid-infrared wavelengths in single-crystalline aluminum nitride waveguides. Tunable dispersive waves are observed at the mid-infrared regime by precisely controlling the waveguide widths. In addition, ultraviolet light is generated through cascaded second-harmonic generation in the modal phase-matched waveguides. Numerical simulation indicates a high degree of coherence of the generated spectrum at around the telecom pump and two dispersive waves. Our results establish a reliable path for multiple octave supercontinuum comb generation in single-crystalline aluminum nitride to enable applications including precision frequency metrology and spectroscopy.

Photonic Dissipation Control for Kerr Soliton Generation in Strongly Raman-Active Media.

Microcavity solitons enable miniaturized coherent frequency comb sources. However, the formation of microcavity solitons can be disrupted by stimulated Raman scattering, particularly in the emerging crystalline microcomb materials with high Raman gain. Here, we propose and implement dissipation control-tailoring the energy dissipation of selected cavity modes-to purposely raise or lower the threshold of Raman lasing in a strongly Raman-active lithium niobate microring resonator and realize on-demand soliton mode locking or Raman lasing. Numerical simulations are carried out to confirm our analyses and agree well with experiment results. Our work demonstrates an effective approach to address strong stimulated Raman scattering for microcavity soliton generation.

Myxofibrosarcoma of the mandible: a case report and review of the literature.

BACKGROUND: Myxofibrosarcoma (MFS) is a soft tissue sarcoma that commonly occurs in late adult life. It is mainly located in the subcutaneous soft tissues of extremities characterized by a high recurrence rate at the original site. MFS of the head and neck is rare, while it occurs in the maxilla and mandible is extremely rare. CASE PRESENTATION: We report a case of MFS of the mandible in a 51-year-old female who presented with a painless gingival swelling and mobile, super-erupted right mandibular second and third molars. Panoramic x-ray and maxillofacial CT revealed an ill-defined radiolucent lesion surrounding the mandibular molars giving a teeth-floating-in-air appearance. Histopathological examination showed scattered spindle and stellate cells with mild atypia distributed in the myxoid stroma. Only a few mitotic figures were identified and no area of tissue necrosis was found. The characteristic thin-walled and curvilinear vasculature were prominent. Immunohistochemistry analysis revealed the tumor cells being positive for vimentin and vascular CD31. CK, S-100, P63, HHF-35 stains were negative. The labeling index of Ki-67 was about 30%. Based on the histopathological and immunohistochemical examinations, the diagnosis of a low-grade MFS was established. This patient underwent a radical segmental excision with a 2-cm margin, supraomohyoid neck dissection and immediate reconstruction of the mandibular continuity defect with a fibular osteocutaneous free flap. This patient has been followed for 20 months to date and has remained disease free. CONCLUSIONS: This report describes a rare case of MFS of the mandible. Recognizing the histopathological features of MFS and applying the appropriate immunohistochemical examinations are crucial in establishing the correct diagnosis. Our case may provide diagnosis and treatment experiences of MFS occurs in the mandible.

Stokes and anti-Stokes Raman scatterings from frequency comb lines in poly-crystalline aluminum nitride microring resonators.

In optical microresonators, stimulated Raman scattering (SRS) competes with four-wave mixing process and impact Kerr comb generation. Here, we demonstrate Raman frequency combs in poly-crystalline aluminum nitride (AlN) microring resonators. The Raman shifts at transverse-electric (TE) and transverse-magnetic (TM) polarizations are characterized from AlN straight waveguides using backscattering geometries. In poly-crystalline AlN microring resonators, the frequency matching of cavity resonances with broad Raman gain enhances the SRS and leads to Raman-assisted frequency combs. As a result, comb lines near Raman scattering regions of AlN are generated.

Octave-spanning supercontinuum generation in nanoscale lithium niobate waveguides.

We demonstrate octave-spanning supercontinuum generation in unpoled lithium niobate waveguides, which are engineered to possess anomalous dispersion and pumped by a turn-key femtosecond laser centered at 1560 nm. Tunable dispersive waves and strong phase-matched second-harmonic generation are both observed by controlling the widths of the waveguides. The major features of the experimental spectra are reproduced by numerical modeling of the generalized nonlinear Schrödinger equation, which can be used to guide waveguide designs for tailoring the supercontinuum spectrum. Our results identify a path to a simple and integrable supercontinuum source in lithium niobate nanophotonic platform and will enable new capabilities in precision frequency metrology.

Soliton microcomb generation at 2 µm in z-cut lithium niobate microring resonators.

Chip-based soliton frequency combs have been demonstrated on various material platforms, offering broadband, mutually coherent, and equally spaced frequency lines desired for many applications. Lithium niobate (LN), possessing both second- and third-order optical nonlinearities, as well as integrability on insulating substrates, has emerged as a novel source for microcomb generation and controlling. Here we demonstrate mode-locked soliton microcombs generated around 2 µm in a high-Q z-cut LN microring resonator. The intracavity photorefractive effect is found to be still dominant over the thermal effect in the 2 µm region, which facilitates direct accessing soliton states in the red-detuned regime, as reported in the telecom band. We also find that intracavity stimulated Raman scattering is greatly suppressed when moving the pump wavelength from the telecom band to 2 µm, thus alleviating Raman-Kerr comb competition. This Letter expands mode-locked LN microcombs to 2 µm, and could enable a variety of potential applications based on LN nanophotonic platform.

High-fidelity cavity soliton generation in crystalline AlN micro-ring resonators.

Chip-scale mode-locked dissipative Kerr solitons have been realized on various materials platforms, making it possible to achieve a miniature, highly coherent frequency comb source with high repetition rates. Aluminum nitride (AlN), an appealing nonlinear optical material having both Kerr (χ3), and Pockels (χ2) effects, has immerse potential for comb self-referencing without the need for external harmonic generators. However, cavity soliton states have not yet been achieved in AlN microresonators. Here, we demonstrate mode-locked Kerr cavity soliton generation in a crystalline AlN microring resonator. By utilizing ultrafast tuning of the pump frequency through single-sideband modulation, in combination with an optimized wavelength scan and pump power-ramp patterns, we can deterministically elongate a ∼400 ns short-lived soliton to a time span as long as we wish to hold it.

Aluminum nitride-on-sapphire platform for integrated high-Q microresonators.

We demonstrate aluminum nitride (AlN) on sapphire as a novel platform for integrated optics. High-confinement AlN microring resonators are realized by adopting a partially etched (pedestal) waveguide to relax the required etching selectivity for exact pattern transfer. A wide taper is employed at the chip end facets to ensure a low fiber-to-chip coupling loss of ~2.8 dB/facet for both transverse-electric (TE) and transverse-magnetic (TM) modes. Furthermore, the intrinsic quality factors (Qint) recorded with a high-resolution linewidth measurement are up to ~2.5 and 1.9 million at telecom band for fundamental TE00 and TM00 modes, corresponding to a low intracavity propagation loss of ~0.14 and 0.2 dB/cm as well as high resonant buildup of 473 and 327, respectively. Such high-Q AlN-on-sapphire microresonators are believed to be very promising for on-chip nonlinear optics.

Role of Notch Signaling in the Physiological Patterning of Posterofrontal and Sagittal Cranial Sutures.

BACKGROUND: The mutations in a Notch signaling ligand, jagged 1, are associated with unilateral coronal craniosynostosis in humans. However, the underlying mechanisms of Notch signaling in cranial suture biology still remain unclear. METHODS: The temporal and spatial patterns of Notch signaling expression were examined in the posterofrontal and sagittal sutures of Sprague-Dawley rats by real-time quantitative reverse-transcription polymerase chain reaction at postnatal ages of 2, 15, and 25 days. The role of Notch signaling in the proliferation and differentiation of osteoblasts isolated from calvarial was examined in vitro by EdU incorporation assays and real-time quantitative reverse-transcription polymerase chain reaction after activating and inhibiting Notch signaling. RESULTS: The mRNA levels of Notch family members (including Jagged 1, Delta 1, 3, 4, Notch 1-4, Hes 1, and Hes 5) decreased during the posterofrontal cranial suture fusion in rat. However, in the patent sagittal sutures, the mRNA levels of Notch family members (Jagged 2, Delta 1, Notch 1, Notch 3, Hes 5, and Hey 1) increased during suture development. The EdU incorporation assays revealed that the induction of Notch signaling in calvaria osteobalsts using Jagged 1 promoted the proliferation rates in those cells in vitro. Further studies showed that activation of Notch signaling calvaria osteobalsts using Jagged 1 led to the suppression of late osteogenetic markers such as type I collagen and osteocalcin. CONCLUSIONS: The regulation of Notch signaling is of crucial importance during the physiological patterning of posterofrontal and sagittal cranial sutures. Thus, targeting this pathway may prove significant for the development of future therapeutic applications in craniosynostosis.

Broadband tunable microwave photonic phase shifter with low RF power variation in a high-Q AlN microring.

An all-optically tunable microwave photonic phase shifter is demonstrated based on an epitaxial aluminum nitride (AlN) microring with an intrinsic quality factor of 3.2×106. The microring adopts a pedestal structure, which allows overcoupling with 700 nm gap size and facilitates the fabrication process. A phase shift for broadband signals from 4 to 25 GHz is demonstrated by employing the thermo-optic effect and the separate carrier tuning technique. A phase tuning range of 0°-332° is recorded with a 3 dB radio frequency (RF) power variation and 48 mW optical power consumption. In addition, AlN exhibits intrinsic second-order optical nonlinearity. Thus, our work presents a novel platform with a low propagation loss and the capability of electro-optic modulation for applications in integrated microwave photonics.

Intra-articular injection of kartogenin promotes fibrocartilage stem cell chondrogenesis and attenuates temporomandibular joint osteoarthritis progression.

Introduction: Kartogenin (KGN) is a small-molecule compound that has been reported to improve the chondrogenic differentiation of mesenchymal stem cells in vitro and to alleviate knee joint osteoarthritis in animal models. However, whether KGN has any effect on temporomandibular joint osteoarthritis (TMJOA) remains unclear. Methods: We first performed partial temporomandibular joint (TMJ) discectomy to induce TMJOA in rats. Histological analysis, tartrate-resistant acid phosphatase staining, and immunohistochemistry were used to assess the therapeutic effect of KGN on TMJOA in vivo. CCK8 and pellet cultures were used to determine whether KGN treatment could promote the proliferation and differentiation of FCSCs in vitro. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine the expression of aggrecan, Col2a1, and Sox9 in FCSCs. Furthermore, we performed western blot to analysis the effect of KGN treatment on the expression of Sox9 and Runx2 in FCSCs. Results and discussion: Histological analysis, tartrate-resistant acid phosphatase staining, and immunohistochemistry showed that intra-articular injection of KGN attenuated cartilage degeneration and subchondral bone resorption in vivo. Further analyses of the underlying mechanisms revealed that KGN enhanced chondrocyte proliferation, increased the number of cells in both superficial and proliferative zones of TMJ condylar cartilage in vivo, enhanced the proliferation and chondrogenic differentiation of fibrocartilage stem cells (FCSCs), and upregulated the expression of chondrogenesis-related factors in vitro. Collectively, in our study, KGN was shown to promote FCSC chondrogenesis and restore TMJ cartilage, suggesting that KGN injections might be a potential treatment for TMJOA.

Epigenetic PPARγ preservation attenuates temporomandibular joint osteoarthritis.

OBJECTIVE: Previous studies have demonstrated that PPARγ deficiency is associated with osteoarthritis in the knee joint. However, whether epigenetic PPARγ dysregulation has any effect on temporomandibular joint osteoarthritis (TMJOA) is unknown. This study aims to determine the role and mechanism of epigenetic PPARγ dysregulation in TMJOA. METHODS: Partial TMJ discectomy was performed to induce TMJOA in rat. Primary condylar chondrocytes were isolated, and TNF-α-induced inflammatory condition was created in vitro. The expressions of PPARγ and DNA methyltransferase were investigated in vivo and in vitro. The association of PPARγ and DNA methylation was further studied by treating chondrocytes with DNA demethylation agent 5-Aza-2'-deoxycytidine (5Aza) and transfecting with siRNA of DNA methyltransferase (DNMT)1 and DNMT3a, and the methylation level of PPARγ promoter was evaluated by Bisulfite-sequencing PCR. The chondroprotective effects of 5Aza were explored in vitro and in vivo. RESULTS: PPARγ suppression and upregulated DNMT1/DNMT3a expression exist in TMJOA cartilage in vivo and primary condylar chondrocytes under TNF-α-induced inflammatory conditions in vitro. DNMT1 and DNMT3a elevation contributes to PPARγ-promoter hypermethylation in TMJ chondrocytes under TNF-α-induced inflammation conditions. DNA demethylation intervention by 5Aza protects chondrocytes from inflammation response in vitro. Mechanistically, 5Aza reversed the hypermethylation of the PPARγ promoter and subsequently resulted in PPARγ restoration and decreased expression of cartilage-catabolic factors in chondrocytes. Rat TMJOA model revealed that 5Aza, by reversing PPARγ suppression, effectively attenuated cartilage degeneration and stabilized cartilage homeostasis by balancing anabolic factor and catabolic factor expression. CONCLUSION: Epigenetic PPARγ suppression may play a causal role in TMJOA pathogenesis, which can be alleviated by DNA demethylation with 5Aza treatment. This study provides new insights into the pathogenic mechanism and therapeutic strategy of TMJOA.

Corrigendum: Anesthesia management of patients undergoing off-pump coronary artery bypass grafting: A retrospective study of single center.

[This corrects the article DOI: 10.3389/fsurg.2022.1067750.].

Wnt16 signaling in bone homeostasis and osteoarthristis.

Wnts are secreted cysteine-rich glycoproteins involved in joint development and skeletal homeostasis and have been implicated in the occurrence of osteoarthritis. Over the past decade, Wnt16, a member of the Wnt family, has received widespread attention for its strong association with bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk. In recent years, further studies have shed light on the role of Wnt16 a positive regulator of bone mass and protective regulator of osteoarthritis progression. Transduction mechanisms and crosstalk involving Wnt16 signaling have also been illustrated. More importantly, local Wnt16 treatment has been shown to ease osteoarthritis, inhibit bone resorption, and promote new bone formation in bone defect models. Thus, Wnt16 is now a potential therapeutic target for skeletal diseases and osteoarthritis. This paper reviews our current understanding of the mechanisms by which Wnt16 signaling regulates bone homeostasis and osteoarthritis.

Intra-articular injection of a novel Wnt pathway inhibitor, SM04690, upregulates Wnt16 expression and reduces disease progression in temporomandibular joint osteoarthritis.

Abnormal Wnt signaling has been shown to be involved in the pathogenesis of temporomandibular joint osteoarthritis (TMJOA). Recent studies demonstrates that SM04690, a small-molecule inhibitor of the Wnt signaling pathway, is able to promote cartilage regeneration in a rat model of knee joint osteoarthritis. However, whether SM04690 has any effect on TMJOA is unknown. Here we first performed partial TMJ discectomy to induce TMJOA in rabbit and rat. Histology, TRAP staining, immunohistochemistry and µCT analysis showed intra-articular injection of SM04690 protected condylar cartilage from degeneration and attenuated abnormal subchondral bone remodeling of TMJ condylar in both rabbit and rat model TMJOA. We isolated and cultured primary condylar chondrocytes for in vitro studies to investigate molecular mechanisms and downstream effects of SM04690. We found that SM04690 inhibited the canonical Wnt pathway, upregulated the expression of Wnt16 and cartilage anabolic factors including COL2A1, SOX9 and aggrecan, suppressed the expression of cartilage catabolic factor MMP13 and protected chondrocytes from TNF-α-induced inflammatory response. Previous studies have identified fibrocartilage stem cells (FCSCs) localized within the TMJ condyle superficial zone niche that regenerate cartilage and repair joint injury. Here we showed that intra-articular injection of SM04690 increased the number of the TMJ condyle superficial zone (SZ) cells in vivo. Further in vitro studies revealed that SM04690 enhanced FCSCs chondrogenesis and formation of cartilaginous-like tissue in pellet cultures. Taken together, our work demonstrates that SM04690 treatment might be able to promote FCSCs chondrogenesis and repair TMJ cartilage, highlighting the therapeutic potential of intra-articular injection of SM04690 in TMJOA.

Malignant fibrous histiocytoma of the floor of mouth: a case report and review of the literature.

Malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma in late adulthood and usually occurs in the limbs, trunk, and peritoneum. Less than 10% of MFH cases occur in the head and neck region. The clinical manifestations and pathological features of MFH are atypical, and it is difficult to make a clinical diagnosis. We describe a rare case of MFH of the floor of mouth and provide our diagnosis and treatment experiences. Through this review, we also evaluate the origin, World Health Organization (WHO) classification, clinical presentations, pathological features, treatment methods, and prognosis of MFH. MFH may originate from fibroblasts or primitive mesenchymal cells. MFH was defined as undifferentiated pleomorphic sarcoma in the 2002 WHO classification of bone and soft tissue tumors. The most common manifestation of MFH is a painless enlarging nodule, often without overlying epidermal ulcers. Jaw lesions are usually found after displays of swelling, pain, paresthesia, and loose teeth. MFH is composed of pleomorphic spindle cells, usually with hemorrhage, necrosis, and lymphocyte infiltration. The main treatment method is surgical resection. Moreover, radiotherapy and chemotherapy have certain auxiliary effects. The local recurrence and distant metastasis of MFH are common, and the prognosis is poor. Therefore, determining the histopathological features of MFH and conducting appropriate immunohistochemical examinations are crucial in establishing the correct diagnosis. In-depth study is required in order to have a better understanding of head and neck MFH.

Anesthesia management of patients undergoing off-pump coronary artery bypass grafting: A retrospective study of single center.

Background: To summarize the current practice of anesthesia management for Chinese patients undergoing off-pump coronary artery bypass (OPCAB) surgery at a large-volume cardiovascular center. Materials and methods: The clinical data of consecutive patients undergoing isolated, primary OPCAB surgery during the period from September 2019 to December 2019 were retrospectively analyzed. Patient characteristics, intraoperative data, and short-term outcomes were extracted from the Hospital Information System and the Anesthesia Information Management System. Results: A total of 255 patients who underwent OPCAB surgery were enrolled in the current study. High-dose opioids and short-acting sedatives were the most commonly administrated anesthetics intraoperatively. Pulmonary arterial catheter insertion is frequently performed in patients with serious coronary heart disease. Goal-directed fluid therapy, a restricted transfusion strategy, and perioperative blood management were routinely used. Rational usages of inotropic and vasoactive agents facilitate hemodynamic stability during the coronary anastomosis procedure. Four patients underwent re-exploration for bleeding, but no death was observed. Conclusions: The study introduced the current practice of anesthesia management at the large-volume cardiovascular center, and the short-term outcomes indicated the efficacy and safety of the practice in OPCAB surgery.

The Efficacy and Safety of Remimazolam Tosilate versus Etomidate-Propofol in Elderly Outpatients Undergoing Colonoscopy: A Prospective, Randomized, Single-Blind, Non-Inferiority Trial.

OBJECTIVE: The optimal sedation regime during endoscopy remains controversial, especially for elderly outpatients. In this study, we compared the efficacy and safety between remimazolam tosilate (RT) and etomidate-propofol (EP) in elderly outpatients undergoing colonoscopy. METHODS: A total of 260 elderly outpatients undergoing sedative colonoscopy were randomized into two groups. Patients in the RT group received a 0.075-mg/kg maintenance dose of remimazolam following an initial dose of 0.15 mg/kg, whereas patients in the EP group (10 mL:20 mg etomidate plus 10 mL:100 mg propofol) received a 0.05-mL/kg maintenance dose following an initial dose of 0.1 mL/kg to maintain a Modified Observer's Assessment of Alertness/Sedation score of ≤3 during the procedure. The primary endpoint was the success of the procedure. Secondary endpoints included time metrics, hemodynamics, consumption of fentanyl, etomidate, propofol, and remimazolam, intraoperative body movement, patient and endoscopist satisfaction scores, supplemental dose of sedative and fentanyl, and incidence and severity of adverse events. RESULTS: The procedure success rate was 96.52% in the RT group and 100% in the EP group. The difference in procedure success rate between the RT and EP groups was -3.48% (95% confidence interval: -6.81%, -0.15%). Four patients in the RT group required rescue midazolam. Compared with patients in the RT group, the onset time of the EP group was significantly lower (p < 0.05), whereas time to fully alert (p = 0.001), ready for discharge (p = 0.001), and hospital discharge (p = 0.002) were all significantly higher in the EP group. However, there were no significant differences in procedure time (p = 0.846) or cecal intubation time (p = 0.320) between the two groups. Although the frequency of intraoperative body movement was higher in the RT group, the difference was not significant (p = 0.508). There were no significant differences in patients' demographic and baseline characteristics, supplemental doses of sedative and fentanyl, or patient and endoscopist satisfaction scores (p > 0.05). Muscular tremor and pain on injection were recorded more frequently in the EP group (p < 0.05). However, there were no significant differences in hypoxia, respiratory depression, or incidence of postoperative nausea and vomiting. The severity of adverse events was all mild (grade 1) across both groups. CONCLUSION: RT may have non-inferior efficacy and a higher safety profile than EP in elderly outpatients undergoing colonoscopy, which suggests that RT may be more suitable for elderly outpatients undergoing colonoscopy.